KRAS mutations drive adenomatoid odontogenic tumor and are independent of clinicopathological features

Página do item simplificado
dc.creatorBruna Pizziolo Coura
dc.creatorLélia Batista de Souza
dc.creatorManoela Domingues Martins
dc.creatorMarina Gonçalves Diniz
dc.creatorRicardo Santiago Gomez
dc.creatorCarolina Cavalieri Gomes
dc.creatorVanessa Fátima Bernardes
dc.creatorSílvia Ferreira de Sousa
dc.creatorJosiane Alves França
dc.creatorNubia Braga Pereira
dc.creatorHélder Antônio Rebelo Pontes
dc.creatorAline Carvalho Batista
dc.creatorDanyel Elias da Cruz Perez
dc.creatorRicardo Luiz Cavalcanti de Albuquerque Junior
dc.date.accessioned2025-07-25T17:34:51Z
dc.date.accessioned2025-09-09T01:32:19Z
dc.date.available2025-07-25T17:34:51Z
dc.date.issued2019-07-01
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1158/1538-7445.AM2019-4663
dc.identifier.issn1538-7445
dc.identifier.urihttps://hdl.handle.net/1843/83848
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofProceedings of the American Association for Cancer Research Annual Meeting 2019
dc.rightsAcesso Restrito
dc.subjectMutation
dc.subjectEvaluation study
dc.subjectCodon
dc.subjectAssociation
dc.subjectMitogen-Activated Protein Kinases
dc.subjectMAP kinase signaling system
dc.subjectPhosphorus
dc.titleKRAS mutations drive adenomatoid odontogenic tumor and are independent of clinicopathological features
dc.typeArtigo de evento
local.citation.epage4663
local.citation.issue13
local.citation.spage4663
local.description.resumoAdenomatoid odontogenic tumor (AOT) is a benign encapsulated epithelial odontogenic tumor that shows indolent clinical behavior and predilection for young individuals. We have recently reported in a few AOT cases mutations in KRAS, which is a proto-oncogene frequently mutated in cancer types such as lung, pancreas and colorectal adenocarcinomas. We aimed to assess KRAS mutations in the hotspot codons 12, 13 and 61 in a large cohort of AOT samples and to test the association of these mutations with clinical (patients’ age, tumor site, tumor size, follicular or extrafollicular subtypes) and histopathological parameters. A convenience sample of 38 central AOT cases was included in the study. KRAS codon 12 mutations were assessed by TaqMan allele-specific qPCR (p.G12V/R) and/or Sanger sequencing, and codon 13 and 61 mutations were screened by Sanger. Histological tumor capsule thickness was evaluated by morphometric analysis. In addition, the phosphorylated form of the MAPK downstream effector ERK1/2 was investigated. Statistical analysis was carried out to test the association of KRAS mutations with clinicopathological parameters. KRAS c.35G>T mutation, leading to p.G12V, was detected in 15 cases. A novel mutation in AOT, c.34G>C, leading to p.G12R, was detected in 12 cases and the other 11 were wild-type. Codon 12 mutations were not associated with the clinicopathological parameters tested. RAS mutations are known to activate the MAPK pathway and we show AOTs express phosphorylated ERK1/2. In conclusion, a high proportion of AOT (27/38, 71%) have KRAS codon 12 mutations, which occur independently of the clinicopathological features evaluated. Collectively, these findings indicate that KRAS mutations and MAPK pathway activation is a common feature of AOT and some cancer types. Although it is unclear why different codon 12 alleles occur in different disease contexts and the complex interactions between tumor genotype-phenotype need clarification, on the basis of our results the presence of KRAS p.G12V or p.G12R can favor the AOT diagnosis in challenging oral neoplasm cases.
local.identifier.orcidhttps://orcid.org/0000-0002-9987-5311
local.identifier.orcidhttps://orcid.org/0000-0001-8662-5965
local.identifier.orcidhttps://orcid.org/0000-0002-4212-1172
local.identifier.orcidhttps://orcid.org/0000-0001-8770-8009
local.identifier.orcidhttps://orcid.org/0000-0003-1580-4995
local.identifier.orcidhttps://orcid.org/0000-0003-0194-7434
local.identifier.orcidhttps://orcid.org/0000-0001-7820-4749
local.identifier.orcidhttps://orcid.org/0000-0002-6005-783X
local.identifier.orcidhttps://orcid.org/0000-0002-6714-3124
local.publisher.countryBrasil
local.publisher.departmentFAO - DEPARTAMENTO DE CLÍNICA
local.publisher.departmentICB - DEPARTAMENTO DE MORFOLOGIA
local.publisher.departmentICB - DEPARTAMENTO DE PATOLOGIA
local.publisher.initialsUFMG
local.url.externahttps://aacrjournals.org/cancerres/article/79/13_Supplement/4663/636689/Abstract-4663-KRAS-mutations-drive-adenomatoid

Arquivos

Licença do pacote

Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
License.txt
Tamanho:
1.99 KB
Formato:
Plain Text
Descrição:
Baixar

Coleções

Artigo de Periódico

Logo UFMG